Under normal physiological conditions, activated protein C (...

created [InstanceEdit:9930429] Shamovsky, Veronica, 2024-12-03
dbId 9930438
displayName Under normal physiological conditions, activated protein C (...
literatureReference
modified [InstanceEdit:9931718] Shamovsky, Veronica, 2024-12-12
schemaClass Summation
text Under normal physiological conditions, activated protein C (APC) regulates clotting by cleaving factor Va (FVa) at R534 and R334, preventing excessive clot formation. FV R534Q (FV Leiden) and FV A540V (FV Bonn) variants are resistant to APC, impairing its ability to inactivate FVa by cleaving it at residue R534 (Bertina RM et al., 1994; van Stralen KJ et al., 2008; Pezeshkpoor B et al., 2016). The defective cleavage of these FV variants may also interfere with APC-mediated inactivation of factor VIIIa (FVIIIa), where non-activated but APC-cleaved FV functions as an APC cofactor (Váradi K et al., 1996; Pezeshkpoor B et al., 2016). In addition to APC resistance, FVa Bonn (A540V) exhibits increased affinity for factor Xa (FXa) (Pezeshkpoor B et al., 2016), which diminishes APC-mediated cleavage at R534, as FXa and APC share a common exosite on FV (reviewed by Bernardi F, 2016). These conditions may lead to prolonged FVa (and FVIII) activity, enhanced function of the prothrombinase FVa:FXa complex, and sustained thrombin generation, which may increase the risk of developing abnormal blood clots causing venous thromboembolism (VTE) in individuals carrying the FV Leiden or FV Bonn mutation (reviewed by Pastori et al., 1999; Perez-Pujol S et al., 2012; van Cott EM et al., 2016; Albagoush SA et al., 2023; Moore GW et al., 2023).
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